TY  - JOUR
AB  - The precise spatial and temporal control of histone phosphorylations is important for the ordered progression through the different phases of mitosis. The phosphorylation of H2B at S6 (H2B S6ph), which is crucial for chromosome segregation, reaches its maximum level during metaphase and is limited to the inner centromere. We discovered that the temporal and spatial regulation of this modification, as well as its intensity, are governed by the scaffold protein RepoMan and its associated catalytically active phosphatases, PP1α and PP1γ. Phosphatase activity is inhibited at the area of maximal H2B S6 phosphorylation at the inner centromere by site-specific Aurora B-mediated inactivation of the PP1/RepoMan complex. The motor protein Mklp2 contributes to the relocalization of Aurora B from chromatin to the mitotic spindle during anaphase, thus alleviating Aurora B-dependent repression of the PP1/RepoMan complex and enabling dephosphorylation of H2B S6. Accordingly, dysregulation of Mklp2 levels, as commonly observed in tumour cells, leads to the lack of H2B S6 dephosphorylation during early anaphase, which might contribute to chromosomal instability.
AU  - Pfisterer, M.*
AU  - Robert, R.*
AU  - Saul, V.V.*
AU  - Pritz, A.*
AU  - Seibert, M.*
AU  - Feederle, R.
AU  - Schmitz, M.L.*
C1  - 70778
C2  - 55889
CY  - 6-9 Carlton House Terrace, London Sw1y 5ag, England
TI  - The Aurora B-controlled PP1/RepoMan complex determines the spatial and temporal distribution of mitotic H2B S6 phosphorylation.
JO  - Open Biol.
VL  - 14
IS  - 5
PB  - Royal Soc
PY  - 2024
ER  - 

TY  - JOUR
AB  - In processes such as development and regeneration, where large cellular and tissue rearrangements occur, cell fate and behaviour are strongly influenced by tissue mechanics. While most well-established tools probing mechanical properties require an invasive sample preparation, confocal Brillouin microscopy captures mechanical parameters optically with high resolution in a contact-free and label-free fashion. In this work, we took advantage of this tool and the transparency of the highly regenerative axolotl to probe its mechanical properties in vivo for the first time. We mapped the Brillouin frequency shift with high resolution in developing limbs and regenerating digits, the most studied structures in the axolotl. We detected a gradual increase in the cartilage Brillouin frequency shift, suggesting decreasing tissue compressibility during both development and regeneration. Moreover, we were able to correlate such an increase with the regeneration stage, which was undetected with fluorescence microscopy imaging. The present work evidences the potential of Brillouin microscopy to unravel the mechanical changes occurring in vivo in axolotls, setting the basis to apply this technique in the growing field of epimorphic regeneration.
AU  - Riquelme-Guzmán, C.*
AU  - Beck, T.*
AU  - Edwards-Jorquera, S.*
AU  - Schlüßler, R.*
AU  - Müller, P.*
AU  - Guck, J.*
AU  - Möllmert, S.*
AU  - Sandoval-Guzmán, T.
C1  - 65546
C2  - 52732
TI  - In vivo assessment of mechanical properties during axolotl development and regeneration using confocal Brillouin microscopy.
JO  - Open Biol.
VL  - 12
IS  - 6
PY  - 2022
ER  - 

TY  - JOUR
AB  - It is undeniably one of the greatest findings in biology that (with some very minor exceptions) every cell in the body possesses the whole genetic information needed to generate a complete individual. Today, this concept has been so thoroughly assimilated that we struggle to still see how surprising this finding actually was: all cellular phenotypes naturally occurring in one person are generated from genetic uniformity, and thus are per definition epigenetic. Transcriptional mechanisms are clearly critical for developing and protecting cell identities, because a mis-expression of few or even single genes can efficiently induce inappropriate cellular programmes. However, how transcriptional activities are molecularly controlled and which of the many known epigenomic features have causal roles remains unclear. Today, clarification of this issue is more pressing than ever because profiling efforts and epigenome-wide association studies (EWAS) continuously provide comprehensive datasets depicting epigenomic differences between tissues and disease states. In this commentary, we propagate the idea of a widespread follow-up use of epigenome editing technology in EWAS studies. This would enable them to address the questions of which features, where in the genome, and which circumstances are essential to shape development and trigger disease states.
AU  - Bultmann, S.*
AU  - Stricker, S.H.
C1  - 53480
C2  - 44588
CY  - 6-9 Carlton House Terrace, London Sw1y 5ag, England
TI  - Entering the post-epigenomic age: Back to epigenetics.
JO  - Open Biol.
VL  - 8
IS  - 3
PB  - Royal Soc
PY  - 2018
ER  - 

TY  - JOUR
AB  - It is undeniably one of the greatest findings in biology that (with some very minor exceptions) every cell in the body possesses the whole genetic information needed to generate a complete individual. Today, this concept has been so thoroughly assimilated that we struggle to still see how surprising this finding actually was: all cellular phenotypes naturally occurring in one person are generated from genetic uniformity, and thus are per definition epigenetic. Transcriptional mechanisms are clearly critical for developing and protecting cell identities, because a mis-expression of few or even single genes can efficiently induce inappropriate cellular programmes. However, how transcriptional activities are molecularly controlled and which of the many known epigenomic features have causal roles remains unclear. Today, clarification of this issue is more pressing than ever because profiling efforts and epigenome-wide association studies (EWAS) continuously provide comprehensive datasets depicting epigenomic differences between tissues and disease states. In this commentary, we propagate the idea of a widespread follow-up use of epigenome editing technology in EWAS studies. This would enable them to address the questions of which features, where in the genome, and which circumstances are essential to shape development and trigger disease states.
AU  - Schallenberg, S.*
AU  - Kretschmer, K.
C1  - 53825
C2  - 45033
CY  - 6-9 Carlton House Terrace, London Sw1y 5ag, England
TI  - New insight into type 1 diabetes development: resolving early diabetogenic CD4+ T cell responses that precede seroconversion.
JO  - Open Biol.
VL  - 6
IS  - 3
PB  - Royal Soc
PY  - 2018
ER  - 

TY  - JOUR
AB  - Immortal hepatocyte cell lines are widely used to elucidate insulin-dependent signalling pathways and regulation of hepatic metabolism, although the often tumorigenic origin might not represent the metabolic state of healthy hepatocytes. We aimed to investigate if murine cell line AML12 and human cell line THLE-2, which are derived from healthy liver cells, are comparable to hepatoma cell line HepG2 for studying acute insulin signalling and expression of gluconeogenic enzymes and hepatokines. Insulin responsiveness of AML12 and THLE-2 cells was impaired when cells were cultured in the recommended growth medium, but comparable with HepG2 cells by using insulin-deficient medium. THLE-2 cells showed low abundance of insulin receptor, while protein levels in HepG2 and AML12 were comparable. AML12 and THLE-2 cells showed only low or nondetectable transcript levels of G6PC and PCK1. Expression of ANGPTL4 was regulated similarly in HepG2 and AML12 cells upon peroxisome proliferator-activated receptor delta activation but only HepG2 cells resemble the in vivo regulation of hepatic ANGPTL4 by cAMP. Composition of the culture medium and protein expression levels of key signalling proteins should be considered when AML12 and THLE-2 are used to study insulin signalling. With regard to gluconeogenesis and hepatokine expression, HepG2 cells appear to be closer to the in vivo situation despite the tumorigenic origin.
AU  - Sefried, S.*
AU  - Häring, H.-U.
AU  - Weigert, C.
AU  - Eckstein, S.S.*
C1  - 54644
C2  - 45733
CY  - 6-9 Carlton House Terrace, London Sw1y 5ag, England
TI  - Suitability of hepatocyte cell lines HepG2, AML12 and THLE-2 for investigation of insulin signalling and hepatokine gene expression.
JO  - Open Biol.
VL  - 8
IS  - 10
PB  - Royal Soc
PY  - 2018
ER  - 

TY  - JOUR
AB  - It is undeniably one of the greatest findings in biology that (with some very minor exceptions) every cell in the body possesses the whole genetic information needed to generate a complete individual. Today, this concept has been so thoroughly assimilated that we struggle to still see how surprising this finding actually was: all cellular phenotypes naturally occurring in one person are generated from genetic uniformity, and thus are per definition epigenetic. Transcriptional mechanisms are clearly critical for developing and protecting cell identities, because a mis-expression of few or even single genes can efficiently induce inappropriate cellular programmes. However, how transcriptional activities are molecularly controlled and which of the many known epigenomic features have causal roles remains unclear. Today, clarification of this issue is more pressing than ever because profiling efforts and epigenome-wide association studies (EWAS) continuously provide comprehensive datasets depicting epigenomic differences between tissues and disease states. In this commentary, we propagate the idea of a widespread follow-up use of epigenome editing technology in EWAS studies. This would enable them to address the questions of which features, where in the genome, and which circumstances are essential to shape development and trigger disease states.
AU  - van Flaxen, J.*
AU  - Charafeddine, R.A.*
AU  - Ettinger, A.
AU  - Wang, H.*
AU  - Hahn, K.M.*
AU  - Wittmann, T.*
C1  - 53824
C2  - 45028
CY  - 6-9 Carlton House Terrace, London Sw1y 5ag, England
SP  - 382A-382A
TI  - Optical control of EB1 reveals local functions of the microtubule plus TIP complex during cell migration and division.
JO  - Open Biol.
VL  - 114
IS  - 3
PB  - Royal Soc
PY  - 2018
ER  - 

TY  - JOUR
AB  - Viruses interact with multiple host cell factors. Some of these are required to promote viral propagation, others have roles in inhibiting infection. Here, we delineate the function of the cellular factor PHF13 (or SPOC1), a putative HIV-1 restriction factor. Early in the HIV-1 replication cycle PHF13 increased the number of integrated proviral copies and the number of infected cells. However, after HIV-1 integration, high levels of PHF13 suppressed viral gene expression. The antiviral activity of PHF13 is counteracted by the viral accessory protein Vpr, which mediates PHF13 degradation. Altogether, the transcriptional master regulator and chromatin binding protein PHF13 does not have purely repressive effects on HIV-1 replication, but also promotes viral integration. By the functional characterization of the dual role of PHF13 during the HIV-1 replication cycle, we reveal a surprising and intricate mechanism through which HIV-1 might regulate the switch from integration to viral gene expression. Furthermore, we identify PHF13 as a cellular target specifically degraded by HIV-1 Vpr.
AU  - Hofmann, S.
AU  - Dehn, S.*
AU  - Businger, R.*
AU  - Bolduan, S.
AU  - Schneider, M.
AU  - Debyser, Z.*
AU  - Brack-Werner, R.
AU  - Schindler, M.
C1  - 52097
C2  - 43720
CY  - London
TI  - Dual role of the chromatin-binding factor PHF13 in the pre- and post-integration phases of HIV-1 replication.
JO  - Open Biol.
VL  - 7
IS  - 10
PB  - Royal Soc
PY  - 2017
ER  - 

TY  - JOUR
AB  - The majority of T cells encountered by HIV-1 are non-activated and do not readily allow productive infection. HIV-1 Vpr is highly abundant in progeny virions, and induces signalling and HIV-1 LTR transcription. We hence hypothesized that Vpr might be a determinant of non-activated T-cell infection. Virion-delivered Vpr activated nuclear factor of activated T cells (NFAT) through Ca(2+) influx and interference with the NFAT export kinase GSK3β. This leads to NFAT translocation and accumulation within the nucleus and was required for productive infection of unstimulated primary CD4(+) T cells. A mutagenesis approach revealed correlation of Vpr-mediated NFAT activation with its ability to enhance LTR transcription and mediate cell cycle arrest. Upon NFAT inhibition, Vpr did not augment resting T-cell infection, and showed reduced G2/M arrest and LTR transactivation. Altogether, Vpr renders unstimulated T cells more permissive for productive HIV-1 infection and stimulates activation of productively infected as well as virus-exposed T cells. Therefore, it could be involved in the establishment and reactivation of HIV-1 from viral reservoirs and might have an impact on the levels of immune activation, which are determinants of HIV-1 pathogenesis.
AU  - Höhne, K.
AU  - Businger, R.*
AU  - van Nuffel, A.*
AU  - Bolduan, S.
AU  - Koppensteiner, H.
AU  - Baeyens, A.*
AU  - Vermeire, J.*
AU  - Malatinkova, E.*
AU  - Verhasselt, B.*
AU  - Schindler, M.
C1  - 49037
C2  - 41561
CY  - London
TI  - Virion encapsidated HIV-1 Vpr induces NFAT to prime non-activated T cells for productive infection.
JO  - Open Biol.
VL  - 6
IS  - 7
PB  - Royal Soc
PY  - 2016
ER  -